Surrogate selection oversamples expanded T cell clonotypes

Abstract

Inference from immunological data on cells in the adaptive immune system may benefit from modeling specifications that describe variation in the sizes of various clonal sub-populations. We develop one such specification in order to quantify the effects of surrogate selection assays, which we confirm may lead to an enrichment for amplified, potentially disease-relevant T cell clones. Our specification couples within-clonotype birth-death processes with an exchangeable model across clonotypes. Beyond enrichment questions about the surrogate selection design, our framework enables a study of sampling properties of elementary sample diversity statistics; it also points to new statistics that may usefully measure the burden of somatic genomic alterations associated with clonal expansion. We examine statistical properties of immunological samples governed by the coupled model specification, and we illustrate calculations in surrogate selection studies of melanoma and in single-cell genomic studies of T cell repertoires. FundingThis research was supported in part by the National Science Foundation (grant 2023239-DMS), and by grants from the National Institutes of Health: R01 GM102756, P01 CA022443, P01 CA250972, P50 CA278595, UL1 TR002373, P50 CA269011, and P30 CA014520. This work was also supported by resources at the William S. Middleton Memorial Veterans Hospital, Madison, WI, USA, and the UW Carbone Comprehensive Cancer Center. Additional support was provided by Anns Hope Foundation, Taking on Melanoma, the Tim Eagle Memorial, and the Jay Van Sloan Memorial from the Steve Leuthold Family Foundation, philanthropic support in the USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the views of the Dept. of Veterans Affairs or the United States Government.